Hepatitis C virus as a promoter in hepatocarcinogenesis

We investigated the possibility that the hepatitis C virus (HCV) acts as a promoter in hepatocar-cinogenesis. We found that HCV core protein cooperated with H-ras and transformed mouse BALB3T3 cells into a tumorigenic phenotype. We identified several candidate genes, whose expression levels were altered by the expression of HCV core or NS5A protein in the immortalized human hepatocytes, using the methods of differential display, quantitative RT-PCR and cDNA expression array. We examined whether HCV core or NS5A protein affects several signal transduction pathways using an in vivo cis reporting assay system. During the course of the study, we found that HCV core protein specifically activated the interferon-inducible 2′-5′ oligoadenylate synthetase gene in a dose-dependent manner. In addition, we developed a novel selectable reporter assay system for microsatellite instability in cultured cells, and examined the effect of HCV proteins on the frequency of replication errors. The results indicated that the HCV core protein decreased the activity of mismatch repair. Together, these results suggest that HCV proteins play some role in hepatocarcinogenesis.